SEC61A2 encodes a subunit of the SEC61 translocon complex, which forms a gated pore in the endoplasmic reticulum (ER) membrane essential for cotranslational translocation of nascent polypeptides containing signal peptides. The protein functions as a ribosome receptor and transmembrane protein transporter, enabling SRP-dependent protein targeting and translocation across the ER membrane. Beyond its canonical translocation role, SEC61A2 exhibits pleiotropic functions. It participates in circadian-regulated collagen metabolism in skin fibroblasts, with Sec61a2 expression peaking during nighttime in the synthesis/secretion phase 1. SEC61A2 overexpression promotes apoptotic cell death in a p53-independent manner 2, suggesting a role in programmed cell death regulation. Clinically, SEC61A2 has emerged as a genetic locus associated with dementia with Lewy bodies (DLB) pathogenesis. A GWAS in Japanese subjects identified a DHTKD1 locus on chromosome 10 associated with SEC61A2 gene expression that demonstrates causal relationship with cholinesterase levels 3, linking SEC61A2 to DLB susceptibility. Additionally, SEC61A2 genetic variation influences metabolic responses to glucose-insulin-potassium therapy, with specific SNPs associated with potassium response in acute coronary syndrome treatment 4. These findings suggest SEC61A2 functions extend beyond protein translocation to include neurodegenerative disease pathogenesis and metabolic regulation.